Lack of effect of cimetidine on the pharmacokinetics of R(−)− and S(+)‐ ibuprofen.

Abstract

1 To investigate the effect of cimetidine on the pharmacokinetics of R(-)-and S(+)-ibuprofen, six healthy male volunteers received orally 800 mg racemic ibuprofen both in the drug-free state (control phase, C) and on the second day of a 3 day course of oral cimetidine, 1 g daily (treatment phase, T). The two phases (14 days apart) were randomised in a balanced cross-over manner.2 The plasma concentrations of R(-)-and S(+)-ibuprofen were measured by highperformance liquid chromatography (h.p.l.c.). The protein binding of the enantiomers was assessed in a selection of plasma samples from each volunteer. Following alkaline hydrolysis of glucuronide conjugates, the urinary recoveries of ibuprofen and its major metabolites were measured by h.p.l.c. 3 There was no difference (P > 0.05, two-tailed Student's t-test; data expressed as mean ± s.d.) between C and T phases in the total area under the plasma concentration-time curve of R(-)-ibuprofen (C 4514 ± 1063 mg 1-1 min vs T 4665 ± 1435 mg 1-1 min) and S(+)-ibuprofen (C 6460 ± 1063 mg 1-1 min vs T 6886 ± 1207 mg 1-1 min). Similarly, for each enantiomer, there was no difference between the two phases in the terminal half-life, the maximum plasma concentration or the time of its occurrence. 4 Cimetidine treatment had no effect (P > 0.05) on the time-averaged percent unbound in plasma of R(-)-ibuprofen (C 0.419 ± 0.051% vs T 0.435 ± 0.060%) and S(+)-ibuprofen (C 0.643 ± 0.093% vs T 0.633 ± 0.053%). 5 There was no difference (P > 0.05) in the percentage of the administered dose recovered in the urine as ibuprofen plus metabolites (C 84.9 ± 7.3% vs T 87.6 ± 3.9%). 6 The results indicate that the pharmacokinetics of R(-)-and S(+)-ibuprofen after a single oral dose of racemic ibuprofen were not influenced by concurrent cimetidine administration.

Dynamical density functional theory and its application to spinodal decomposition

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“…͑24͒, keeping only terms that are linear in the fluctuation ˜, we obtain. 5,36 ͑ ⌫k B T ͒ Ϫ1 ‫͑˜ץ‬r,t ͒ ‫ץ‬t…”

Spontaneous charging and crystallization of water droplets in oil

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A density-functional theory study of the confined soft ellipsoid fluid

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